State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Sichuan, China.
Microvasc Res. 2010 Jul;80(1):10-7. doi: 10.1016/j.mvr.2009.12.002. Epub 2010 Jan 4.
Combinatorial strategy has been used in therapeutic angiogenesis in animal models of peripheral arterial disease (PAD) and coronary artery disease for decades. Previous studies have shown that basic fibroblast growth factor (FGF-2) and platelet-derived growth factor BB (PDGF-BB) proteins together establish functional and stable vascular networks on mouse corneal and also in animal model of hindlimb ischemia. However, the short half life of protein by single injection is not sufficient to achieve effective dosage, repeated and prolonged injection causes systemic toxicity. Here we study the synergistic effects of FGF-2 and PDGF-BB by intramuscular injection of naked plasmid DNA on therapeutic angiogenesis in rabbit model of hindlimb ischemia. We found that transient delivery of FGF-2 and PDGF-BB naked DNA together resulted in greater increases in capillary growth, collateral formation and popliteal blood flow compared with control and single gene delivery. Our data provided novel evidence of beneficial effects of DNA-based FGF-2 and PDFG-BB on muscle repair after ischemic injury. These findings reveal an alternative therapeutic approach in the treatment of ischemic diseases and even in muscular disorders.
几十年来，组合策略已被用于外周动脉疾病（PAD）和冠状动脉疾病的治疗性血管生成的动物模型中。先前的研究表明，碱性成纤维细胞生长因子（FGF-2）和血小板衍生生长因子 BB（PDGF-BB）蛋白联合在小鼠角膜和后肢缺血动物模型上共同建立了功能和稳定的血管网络。然而，单次注射的蛋白质半衰期短，不足以达到有效剂量，重复和长期注射会引起全身毒性。在这里，我们通过肌肉内注射裸质粒 DNA 研究 FGF-2 和 PDGF-BB 的协同作用对兔后肢缺血模型的治疗性血管生成的影响。我们发现，与对照和单基因转导相比，FGF-2 和 PDGF-BB 裸 DNA 的瞬时共转导导致毛细血管生长、侧支形成和腘血流增加。我们的数据为基于 DNA 的 FGF-2 和 PDFG-BB 对缺血性损伤后肌肉修复的有益作用提供了新的证据。这些发现揭示了治疗缺血性疾病甚至肌肉疾病的另一种治疗方法。
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